当前位置: X-MOL 学术bioRxiv. Cell Biol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Patrolling human SLE haematopoietic progenitors demonstrate enhanced extramedullary colonisation; implications for peripheral tissue injury
bioRxiv - Cell Biology Pub Date : 2021-01-15 , DOI: 10.1101/2021.01.15.426761
Ioannis Kokkinopoulos , Aggelos Banos , Maria Grigoriou , Anastasia Filia , Theodora Manolakou , Themis Alissafi , Nikolaos Malissovas , Ioannis Mitroulis , Panayotis Verginis , Dimitrios T. Boumpas

Systemic Lupus erythematosus (SLE) is an autoimmune disease where bone-marrow-derived haematopoietic cells have a key role in its pathogenesis with accumulating evidence suggesting an aberrant function of haematopoietic stem/progenitor cells (HSPCs). By employing next-generation sequencing, we compared the gene transcription signatures of CD34+ HSPCs deriving from either the bone marrow or HSPCs patrolling the bloodstream of healthy and individuals with SLE, seeking common transcriptional pathways that may have been modified between steady and disease states. Our findings indicate that circulating and bone marrow-derived HSPCs are distinct in steady and diseased states. Non-mobilised, SLE-derived circulating HSPCs demonstrated enhanced engrafting and altered differentiation capacities. Importantly, xenotransplantation of circulating HSPCs in humanised mice showed that human peripheral blood HSPCs possess the ability for extramedullary organ colonisation to the kidneys. SLE CD34+ HSPCs homing and engraftment at extramedullary sites such as the spleen and kidneys may participate in peripheral tissue injury.

中文翻译:

巡逻的人类SLE造血祖细胞显示出髓外定植增强;对周围组织损伤的影响

系统性红斑狼疮(SLE)是一种自身免疫性疾病,其中骨髓来源的造血细胞在其发病机理中起着关键作用,越来越多的证据表明造血干/祖细胞(HSPC)的功能异常。通过采用下一代测序,我们比较了从CD34 + HSPC的基因转录特征,这些CD34 + HSPC来自在健康人群和SLE患者的血液中巡逻的骨髓或HSPC,寻找在稳态和疾病状态之间可能已被修饰的常见转录途径。我们的发现表明,循环和骨髓来源的HSPC在稳定和患病状态下是截然不同的。未动员的SLE衍生的循环HSPC表现出更高的嫁接能力和改变的分化能力。重要的,在人源化小鼠中循环HSPC的异种移植表明,人外周血HSPC具有将髓外器官定植到肾脏的能力。SLE CD34 + HSPC在髓外部位(如脾脏和肾脏)的归巢和植入可能参与周围组织的损伤。
更新日期:2021-01-18
down
wechat
bug